US3803170A - 2-((1-benzylcyclopentyl)imino)pyrrolidine - Google Patents
2-((1-benzylcyclopentyl)imino)pyrrolidine Download PDFInfo
- Publication number
- US3803170A US3803170A US00280048A US28004872A US3803170A US 3803170 A US3803170 A US 3803170A US 00280048 A US00280048 A US 00280048A US 28004872 A US28004872 A US 28004872A US 3803170 A US3803170 A US 3803170A
- Authority
- US
- United States
- Prior art keywords
- benzylcyclopentyl
- pyrrolidine
- imino
- compound
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- ZGGSCVUIKNQWHQ-UHFFFAOYSA-N n-(1-benzylcyclopentyl)-3,4-dihydro-2h-pyrrol-5-amine Chemical compound C1CCCC1(N=C1NCCC1)CC1=CC=CC=C1 ZGGSCVUIKNQWHQ-UHFFFAOYSA-N 0.000 title description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 abstract description 11
- 239000002253 acid Substances 0.000 abstract description 9
- 150000003839 salts Chemical class 0.000 abstract description 9
- 101000740162 Homo sapiens Sodium- and chloride-dependent transporter XTRP3 Proteins 0.000 abstract 1
- 102100037189 Sodium- and chloride-dependent transporter XTRP3 Human genes 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 17
- 239000000203 mixture Substances 0.000 description 8
- -1 benzylcyclopentyl Chemical group 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000001841 imino group Chemical group [H]N=* 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 239000003472 antidiabetic agent Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229940126904 hypoglycaemic agent Drugs 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- QYGNDKJRRNVSEC-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-pyrrole Chemical compound COC1=NCCC1 QYGNDKJRRNVSEC-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000012059 conventional drug carrier Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Definitions
- This invention relates to 2 [(1 benzylcyclopentyl)- imino]pyrrolidine and pharmaceutically acceptable acid addition salts thereof useful as hypoglycemic agents.
- novel compound of this invention useful as a hypoglycemic agent is 2-[(1 benzylcyclopentyDimino] pyrrolidine and may be represented by the following Formula I.
- Pharmaceutically acceptable acid addition salts of the base compound of this invention are those of any suitable inorganic or organic acid.
- Suitable inorganic acids are, for example, hydrochloric, hydrobromic, sulfuric, or phosphoric acids and the like.
- Suitable organic acids are, for example, carboxylic acids such as acetic, propionic, glycolic, lactic, pyruvic, malonic, succinic, fumaric, malic, tartaric, citric, ascorbic, maleic, hydroxymaleic, benzoic, hydroxybenzoic, phenylacetic, cinnamic, salicylic, 2-phenoxybenzoic and the like, or sulfonic acid and the like.
- the compound of this invention is named and represented as a substituted 2 iminoperhydroazacarbocyclic, as represented by Formula I. It is known however that this compound as an acid addition salt may also be represented by the tautomeric form illustrated by the following anion- 3,803,170 Patented Apr. 9, 1974 "ice anion- (Formula III) It is understood that this invention relates to the novel compound represented or named in either tautomeric form as illustrated by Formulas I and II.
- novel compound of this invention and pharmaceutically acceptable acid addition salts thereof posses useful hypoglycemic properties.
- hydrochloride salt of 2 [(1 benzylcyclopentyl)imino]pyrrolidine administered to glucose-primed rats at 100, 50, 25, and 12.5 mg./kg. (milligrams per kilogram) orally reduced plasma glucose respectively by 60, 42, 26, and 21 percent of control.
- the novel compound of this invention can be administered to animals, mammals, and humans either alone or in the form of pharmaceutical preparations which contain the novel compound suitable for oral or parenteral administration.
- Pharmaceutical preparations containing the novel compound and conventional pharmaceutical carriers can be employed in unit dosage forms such as solids, for example tablets, capsules and pills, or liquid solutions, suspensions, or elixirs for oral administration, or liquid solutions, suspensions, emulsions and the like for parenteral use.
- the quantity of compound administered can vary over a wide range to provide from about 1.0 mg./kg. to about mg./kg. of body weight of the patient per day to achieve the desired efiect.
- Unit doses of this compound can contain, for example, from about 25 to 500 mg. of the compound and may be administered, for example, 1 to 4 times daily.
- the compound of this invention may be prepared by reacting an excess of a compound of the formula N 2 lower alkyl-R-C (CH2)! Formula V in a manner similar to that reported by R. E. 'Benson and T. L. Cairns, I. Am. Chem. Soc. 70, 2115-8 (1948).
- R represents oxygen or divalent sulfur.
- the reaction is carried out with the compound of Formula IV wherein R represents oxygen.
- lower alcohol solvents such as methanol, ethanol, isopropyl alcohol and the like may be employed.
- the hydrochloride salt of the amine as represented by Formula V be used in the reaction.
- the temperature of the reaction varies from 0 to 40 C., and the preferred temperature is about 15 to 25 C.
- the reaction time varies from 15 to 60 days.
- hydrochloride salt of 2-[(1-benzylcyclopentyl)- iminoJpyrrolidine can be converted to the free base with a solution of 2 N sodium hydroxide.
- Other salt forms can be obtained by addition of the appropriate acid to the free base.
- EXAMPLE 2 An illustrative composition for tablets is the following:
- a granulation obtained upon mixing lactose with the starch and granulated starch paste is dried, screened and mixed with the active ingredient, that is, (a), and magnesium stearate. The mixture is compressed into tablets weighing 150 mg. each.
- EXAMPLE 3 4 The formulation is prepared by passing the dry powders of (a) and (b) through a fine mesh screen and mixing them well. The powder is then filled into No. 0 hard gelatin capsules at a net fill of 235 mg. per capsule.
- EXAMPLE 4 An illustrative composition for a parenteral injection is the following wherein the quantities are on a weight to volume basis.
- the composition is prepared by dissolving the active ingredient and sufiicient sodium chloride in water for injection to render the solution isotonic.
- the composition may 'be dispensed in a single ampule containing mg. of the active ingredient for multiple dosage or in 10 ampules for a single dose.
- a compound of claim 1 which is 2-[(l-benzylcyclopentyl)imino] pyrrolidine hydrochloride.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US00280048A US3803170A (en) | 1972-08-11 | 1972-08-11 | 2-((1-benzylcyclopentyl)imino)pyrrolidine |
GB2046073A GB1367597A (en) | 1972-08-11 | 1973-04-30 | Pyrrolidine derivative |
ZA732922A ZA732922B (en) | 1972-08-11 | 1973-04-30 | Pyrrolidene derivative |
IL42201A IL42201A (en) | 1972-08-11 | 1973-05-04 | 2-((1-benzylcyclopentyl)-imino)pyrrolidine |
CA170,699A CA976973A (en) | 1972-08-11 | 1973-05-08 | Pyrrolidine derivative |
DE2324633A DE2324633A1 (de) | 1972-08-11 | 1973-05-16 | 2-eckige klammer auf (1-benzylcyclopentyl)-imino eckige klammer zu -pyrrolidin, verfahren zu seiner herstellung und diese verbindung enthaltende therapeutische zubereitungen |
JP48054180A JPS4945064A (enrdf_load_html_response) | 1972-08-11 | 1973-05-17 | |
AU55933/73A AU467863B2 (en) | 1972-08-11 | 1973-05-21 | 2-[ci-benzylcyclopentyl) imino] |
NL7308928A NL7308928A (enrdf_load_html_response) | 1972-08-11 | 1973-06-27 | |
CH1086073A CH588461A5 (enrdf_load_html_response) | 1972-08-11 | 1973-07-25 | |
FR7329216A FR2195445B1 (enrdf_load_html_response) | 1972-08-11 | 1973-08-09 | |
DK442373AA DK135502B (da) | 1972-08-11 | 1973-08-10 | Analogifremgangsmåde til fremstilling af 2-((1-benzylcyclopentyl)-imino)-pyrrolidin eller dens farmaceutisk acceptable syreadditionssalte |
BE134467A BE803483A (fr) | 1972-08-11 | 1973-08-10 | Derives de pyrrolidine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US00280048A US3803170A (en) | 1972-08-11 | 1972-08-11 | 2-((1-benzylcyclopentyl)imino)pyrrolidine |
Publications (1)
Publication Number | Publication Date |
---|---|
US3803170A true US3803170A (en) | 1974-04-09 |
Family
ID=23071419
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US00280048A Expired - Lifetime US3803170A (en) | 1972-08-11 | 1972-08-11 | 2-((1-benzylcyclopentyl)imino)pyrrolidine |
Country Status (12)
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5010072A (en) * | 1988-06-28 | 1991-04-23 | Merrell Dow Pharmaceuticals Inc. | Lactamimides as calcium antagonists |
US5082837A (en) * | 1988-06-28 | 1992-01-21 | Merrell Dow Pharmaceuticals | Lactamimides as calcium antagonists |
US5198433A (en) * | 1988-06-28 | 1993-03-30 | Merrell Dow Pharmaceuticals Inc. | Lactamimides as calcium antagonists |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ183570A (en) * | 1976-03-19 | 1979-06-08 | Mcneilab Inc | Heterocyclic guanidine derivatives, having anti-secretory and hypogliycaemic activity |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB913932A (en) * | 1958-03-03 | 1962-12-28 | Rohm & Haas | Iminopyrrolidines |
-
1972
- 1972-08-11 US US00280048A patent/US3803170A/en not_active Expired - Lifetime
-
1973
- 1973-04-30 ZA ZA732922A patent/ZA732922B/xx unknown
- 1973-04-30 GB GB2046073A patent/GB1367597A/en not_active Expired
- 1973-05-04 IL IL42201A patent/IL42201A/en unknown
- 1973-05-08 CA CA170,699A patent/CA976973A/en not_active Expired
- 1973-05-16 DE DE2324633A patent/DE2324633A1/de active Pending
- 1973-05-17 JP JP48054180A patent/JPS4945064A/ja active Pending
- 1973-06-27 NL NL7308928A patent/NL7308928A/xx not_active Application Discontinuation
- 1973-07-25 CH CH1086073A patent/CH588461A5/xx not_active IP Right Cessation
- 1973-08-09 FR FR7329216A patent/FR2195445B1/fr not_active Expired
- 1973-08-10 BE BE134467A patent/BE803483A/xx unknown
- 1973-08-10 DK DK442373AA patent/DK135502B/da unknown
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5010072A (en) * | 1988-06-28 | 1991-04-23 | Merrell Dow Pharmaceuticals Inc. | Lactamimides as calcium antagonists |
US5082837A (en) * | 1988-06-28 | 1992-01-21 | Merrell Dow Pharmaceuticals | Lactamimides as calcium antagonists |
US5198433A (en) * | 1988-06-28 | 1993-03-30 | Merrell Dow Pharmaceuticals Inc. | Lactamimides as calcium antagonists |
Also Published As
Publication number | Publication date |
---|---|
FR2195445B1 (enrdf_load_html_response) | 1976-10-22 |
BE803483A (fr) | 1973-12-03 |
GB1367597A (en) | 1974-09-18 |
DK135502B (da) | 1977-05-09 |
CA976973A (en) | 1975-10-28 |
IL42201A (en) | 1976-02-29 |
FR2195445A1 (enrdf_load_html_response) | 1974-03-08 |
NL7308928A (enrdf_load_html_response) | 1974-02-13 |
IL42201A0 (en) | 1973-07-30 |
ZA732922B (en) | 1974-04-24 |
AU5593373A (en) | 1974-11-21 |
DE2324633A1 (de) | 1974-02-28 |
JPS4945064A (enrdf_load_html_response) | 1974-04-27 |
CH588461A5 (enrdf_load_html_response) | 1977-06-15 |
DK135502C (enrdf_load_html_response) | 1977-10-17 |
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